Purpose: Targeted radiopharmaceutical therapy (RPT) in combination with external beam radiotherapy (EBRT) shows promise as a method to increase tumor control and mitigate potential high-grade toxicities associated with re-treatment for patients with recurrent head and neck cancer. This work establishes a patient-specific dosimetry framework that combines Monte Carlo based dosimetry from the two radiation modalities at the voxel level using deformable image registration (DIR) and radiobiological constructs for patients enrolled in a phase I clinical trial combining EBRT and RPT.
Methods: Serial SPECT/CT patient scans performed at approximately 24-, 48-, 72-, and 168-hours post-injection of 15.6 mCi/m² Iodine-131 containing RPT agent called CLR 131. A clinical EBRT treatment plan was created on a treatment planning CT (TPCT) using RayStation; SPECT/CT images were registered to the TPCT using the Elastix DIR module in 3D Slicer. Monte Carlo EBRT dosimetry was computed using EGSnrc. Deformed SPECT images were used as input to a GEANT4 based RPT dosimetry platform named RAPID. Radiobiological metrics (BED, EQD2) were utilized to sum the two radiation modalities.
Results: The DIR was found to preserve activity concentrations in tumor volumes from SPECT/CT to TPCT; the maximum activity concentration difference was 3.3%. Differences between RayStation and EGSnrc manifested in bony anatomy; gamma analysis resulted in 95% agreement. Based on the RPT absorbed dose, two EBRT fractions were removed from patient’s treatment course. Without partial volume corrections (PVC), the mean EQD2 to the PTV from the EBRT+RPT was -1.5% compared to EBRT alone. When PVC were included, the mean EQD2 to the PTV from EBRT+RPT was +1.1% compared to EBRT alone.
Conclusion: This work demonstrates the clinical utility of performing combined EBRT+RPT dosimetry on TPCTs. Incorporating RPT dose during the optimization of EBRT plans could further improve the quality of treatment plans and reduce dose to normal tissues.
Funding Support, Disclosures, and Conflict of Interest: This project is supported by the Specialized Program of Research Excellence (SPORE) program, through the NIH National Institute for Dental and Craniofacial Research (NIDCR) and National Cancer Institute (NCI), grant P50DE026787. BB and JG are co-founders of Voximetry, Inc., a nuclear medicine dosimetry company in Madison, WI.